Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4DH7PR)

DOT Name	Homeobox protein goosecoid (GSC)
Gene Name	GSC
Related Disease	Adult glioblastoma ( ) Carcinoma ( ) Carcinoma of liver and intrahepatic biliary tract ( ) Glioma ( ) Gonorrhea ( ) Hepatocellular carcinoma ( ) Insomnia ( ) Liver cancer ( ) Malignant glioma ( ) Neoplasm ( ) Short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome ( ) Stomach cancer ( ) Advanced cancer ( ) Cornelia de Lange syndrome ( ) Thrombocytopenia ( ) Glioblastoma multiforme ( ) Gastric cancer ( ) Non-insulin dependent diabetes ( ) Pneumocystis pneumonia ( )
UniProt ID	GSC_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	2DMU
Pfam ID	PF00046
Sequence	MPASMFSIDNILAARPRCKDSVLPVAHSAAAPVVFPALHGDSLYGASGGASSDYGAFYPR PVAPGGAGLPAAVSGSRLGYNNYFYGQLHVQAAPVGPACCGAVPPLGAQQCSCVPTPPGY EGPGSVLVSPVPHQMLPYMNVGTLSRTELQLLNQLHCRRKRRHRTIFTDEQLEALENLFQ ETKYPDVGTREQLARKVHLREEKVEVWFKNRRAKWRRQKRSSSEESENAEKWNKTSSSKA SPEKREEEGKSDLDSDS
Function	Regulates chordin (CHRD). May play a role in spatial programing within discrete embryonic fields or lineage compartments during organogenesis. In concert with NKX3-2, plays a role in defining the structural components of the middle ear; required for the development of the entire tympanic ring. Probably involved in the regulatory networks that define neural crest cell fate specification and determine mesoderm cell lineages in mammals.
Reactome Pathway	Formation of definitive endoderm (R-HSA-9823730 ) Germ layer formation at gastrulation (R-HSA-9754189 )

Molecular Interaction Atlas (MIA) of This DOT

19 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Adult glioblastoma	DISVP4LU	Strong	Biomarker	[1]
Carcinoma	DISH9F1N	Strong	Biomarker	[2]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[3]
Glioma	DIS5RPEH	Strong	Biomarker	[4]
Gonorrhea	DISQ5AO6	Strong	Biomarker	[5]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[3]
Insomnia	DIS0AFR7	Strong	Biomarker	[6]
Liver cancer	DISDE4BI	Strong	Biomarker	[3]
Malignant glioma	DISFXKOV	Strong	Altered Expression	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Short stature-auditory canal atresia-mandibular hypoplasia-skeletal anomalies syndrome	DISITJVT	Strong	Autosomal recessive	[9]
Stomach cancer	DISKIJSX	Strong	Biomarker	[10]
Advanced cancer	DISAT1Z9	moderate	Biomarker	[11]
Cornelia de Lange syndrome	DISEQSXO	moderate	Altered Expression	[12]
Thrombocytopenia	DISU61YW	moderate	Genetic Variation	[12]
Glioblastoma multiforme	DISK8246	Disputed	Biomarker	[13]
Gastric cancer	DISXGOUK	Limited	Biomarker	[10]
Non-insulin dependent diabetes	DISK1O5Z	Limited	Genetic Variation	[14]
Pneumocystis pneumonia	DISFSOM3	Limited	Biomarker	[15]
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⏷ Show the Full List of 19 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

4 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Homeobox protein goosecoid (GSC).	[16]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Homeobox protein goosecoid (GSC).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Homeobox protein goosecoid (GSC).	[18]
Ethanol	DMDRQZU	Approved	Ethanol increases the expression of Homeobox protein goosecoid (GSC).	[20]
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2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Homeobox protein goosecoid (GSC).	[19]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Homeobox protein goosecoid (GSC).	[21]
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References

1	Meta-Analysis and Experimental Validation Identified FREM2 and SPRY1 as New Glioblastoma Marker Candidates.Int J Mol Sci. 2018 May 4;19(5):1369. doi: 10.3390/ijms19051369.
2	Overexpression of goosecoid homeobox is associated with chemoresistance and poor prognosis in ovarian carcinoma.Oncol Rep. 2014 Jul;32(1):189-98. doi: 10.3892/or.2014.3203. Epub 2014 May 20.
3	Changes in S-adenosylmethionine synthetase in human liver cancer: molecular characterization and significance.Hepatology. 1996 Nov;24(5):1090-7. doi: 10.1002/hep.510240519.
4	Bioactive 3,8-Epoxy Iridoids from Valeriana jatamansi.Chem Biodivers. 2019 May;16(5):e1800474. doi: 10.1002/cbdv.201800474. Epub 2019 Apr 8.
5	Glucocorticoids decrease the numbers and activation of mast cells by inducing the transactivation receptors of AGEs.J Leukoc Biol. 2019 Jan;105(1):131-142. doi: 10.1002/JLB.3A0917-364RR. Epub 2018 Sep 10.
6	Insomnia-perchance a dream? Results from a NREM/REM sleep awakening study in good sleepers and patients with insomnia.Sleep. 2018 May 1;41(5). doi: 10.1093/sleep/zsy032.
7	Preferential expression of functional IL-17R in glioma stem cells: potential role in self-renewal.Oncotarget. 2016 Feb 2;7(5):6121-35. doi: 10.18632/oncotarget.6847.
8	Establishment of malignantly transformed dendritic cell line SU3-ihDCTC induced by Glioma stem cells and study on its sensitivity to resveratrol.BMC Immunol. 2018 Feb 2;19(1):7. doi: 10.1186/s12865-018-0246-z.
9	SAMS, a syndrome of short stature, auditory-canal atresia, mandibular hypoplasia, and skeletal abnormalities is a unique neurocristopathy caused by mutations in Goosecoid. Am J Hum Genet. 2013 Dec 5;93(6):1135-42. doi: 10.1016/j.ajhg.2013.10.027. Epub 2013 Nov 27.
10	Reciprocal Reprogramming of Cancer Cells and Associated Mesenchymal Stem Cells in Gastric Cancer.Stem Cells. 2019 Feb;37(2):176-189. doi: 10.1002/stem.2942. Epub 2018 Nov 23.
11	Olea europaea leaf extract and bevacizumab synergistically exhibit beneficial efficacy upon human glioblastoma cancer stem cells through reducing angiogenesis and invasion in vitro.Biomed Pharmacother. 2017 Jun;90:713-723. doi: 10.1016/j.biopha.2017.04.022. Epub 2017 Apr 15.
12	Genomic organisation of the human chordin gene and mutation screening of candidate Cornelia de Lange syndrome genes.Hum Genet. 1999 Jul-Aug;105(1-2):104-11. doi: 10.1007/s004399900068.
13	Truncated Glioma-Associated Oncogene Homolog 1 (tGLI1) Mediates Mesenchymal Glioblastoma via Transcriptional Activation of CD44.Cancer Res. 2018 May 15;78(10):2589-2600. doi: 10.1158/0008-5472.CAN-17-2933. Epub 2018 Feb 20.
14	Evaluation of four novel genetic variants affecting hemoglobin A1c levels in a population-based type 2 diabetes cohort (the HUNT2 study).BMC Med Genet. 2011 Feb 4;12:20. doi: 10.1186/1471-2350-12-20.
15	Transcriptomic and Proteomic Approaches to Finding Novel Diagnostic and Immunogenic Candidates in Pneumocystis.mSphere. 2019 Sep 4;4(5):e00488-19. doi: 10.1128/mSphere.00488-19.
16	Effects of lithium and valproic acid on gene expression and phenotypic markers in an NT2 neurosphere model of neural development. PLoS One. 2013;8(3):e58822.
17	Evaluation of a human iPSC-derived BBB model for repeated dose toxicity testing with cyclosporine A as model compound. Toxicol In Vitro. 2021 Jun;73:105112. doi: 10.1016/j.tiv.2021.105112. Epub 2021 Feb 22.
18	Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
19	Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
20	Chronic ethanol exposure increases goosecoid (GSC) expression in human embryonic carcinoma cell differentiation. J Appl Toxicol. 2014 Jan;34(1):66-75.
21	Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.